EBF1-Mediated Upregulation of Ribosome Assembly Factor PNO1 Contributes to Cancer Progression by Negatively Regulating the p53 Signaling Pathway

Shen, Aling; Chen, Youqin; Liu, Liya; Huang, Yue; Chen, Hongwei; Qi, Fei; Lin, Jiumao; Shen, Zhiqing; Wu, Xiangyan; Wu, Meizhu; Li, Qiongyu; Qiu, Liman; Yu, Na; Sferra, Thomas J.; Peng, Jun

doi:10.1158/0008-5472.can-18-3238

Cited by 55 publications

(95 citation statements)

References 45 publications

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“…However, whether mTORC1/RAPTOR signaling regulates oncogenic function through transcriptional activation of ribosome assembly factors has not been elucidated. PNO1, a ribosome assembly factor, has been reported to contribute to CRC progression by negatively regulating the p53 signaling pathway . This study encouraged us to explore the latent relationship between mTORC1/RAPTOR signaling and ribosome assembly factors in tumorigenesis.…”

Section: Discussionmentioning

confidence: 97%

“…When analyzing the level of protein expression, negative was defined as no or weak staining in cells, whereas positive expression was defined as distinct or strong staining in more than 20% cells . High or low expression level of RAPTOR was assessed as previously described . The relationship between RAPTOR expression and clinicopathological characteristics was analyzed using a Chi‐square test.…”

Section: Methodsmentioning

confidence: 99%

“…22 High or low expression level of RAPTOR was assessed as previously described. 17 The relationship between RAPTOR expression and clinicopathological characteristics was analyzed using a Chi-square test.…”

Section: Immunohistochemistrymentioning

confidence: 99%

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RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1

et al. 2019

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Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). It has been reported that the ribosome assembly factor Urb1 acts downstream of mTORC1/raptor signaling and contributes to digestive organ development in zebrafish. Previously, we highlighted that URB1 was overexpressed in CRC. Here, we assessed the mTORC1/regulatory associated protein with mTOR (RAPTOR)‐URB1 axis in CRC tumorigenesis. We found that RAPTOR was overexpressed in CRC tissues and cell lines, was a favorable predictor in patients with CRC, and positively correlated with URB1. Silencing of RAPTOR suppressed CRC cell proliferation and migration and induced cell cycle arrest and apoptosis in vitro and inhibited xenograft growth in vivo. Moreover, ectopic overexpression of RAPTOR exerted an inverse biological phenotype. Knockdown of RAPTOR quenched mTORC1 activity and reduced the expression of URB1 and cyclinA2 (CCNA2). In contrast, overexpression of RAPTOR activated mTORC1 and upregulated URB1 and CCNA2. Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Thus, RAPTOR promoted CRC proliferation, migration, and cell cycle progression by inducing mTORC1 signaling and transcriptional activation of both URB1 and CCNA2. Taken together, we concluded that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for CRC.

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Section: Discussionmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

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RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1

et al. 2019

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“…Also, the expression of NFATC1 and STAT1 are associated with PD-L1 in bladder urothelial carcinoma [19]. Among other transcription factors, EBF1 has been reported in a variety of tumors and immune-related diseases [20][21][22]. DNA sequencing and qRT-PCR of urine specimens confirmed that EBF1 was different between bladder urothelial carcinoma and normal tissues [23], but this difference did not exist in upper urinary tract tumors [24], suggesting that EBF1 may be bladder-specific.…”

Section: Discussionmentioning

confidence: 94%

Identification of Prognostic Immune Genes in Bladder Urothelial Carcinoma

Sun

Zhang

et al. 2020

BioMed Research International

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Background. The aim of this study is to identify possible prognostic-related immune genes in bladder urothelial carcinoma and to try to predict the prognosis of bladder urothelial carcinoma based on these genes. Methods. The Cancer Genome Atlas (TCGA) expression profile data and corresponding clinical traits were obtained. Differential gene analysis was performed using R software. Reactome was used to analyze the pathway of immune gene participation. The differentially expressed transcription factors and differentially expressed immune-related genes were extracted from the obtained list of differentially expressed genes, and the transcription factor-immune gene network was constructed. To analyze the relationship between immune genes and clinical traits of bladder urothelial carcinoma, a multifactor Cox proportional hazards regression model based on the expression of immune genes was established and validated. Results. Fifty-eight immune genes were identified to be associated with the prognosis of bladder urothelial carcinoma. These genes were enriched in Cytokine Signaling in Immune System, Signaling by Receptor Tyrosine Kinases, Interferon alpha/beta signaling, and other immune related pathways. Transcription factor-immune gene regulatory network was established, and EBF1, IRF4, SOX17, MEF2C, NFATC1, STAT1, ANXA6, SLIT2, and IGF1 were screened as hub genes in the network. The model calculated by the expression of 16 immune genes showed a good survival prediction ability (p<0.05 and AUC = 0.778). Conclusion. A transcription factor-immune gene regulatory network related to the prognosis of bladder urothelial carcinoma was established. EBF1, IRF4, SOX17, MEF2C, NFATC1, STAT1, ANXA6, SLIT2, and IGF1 were identified as hub genes in the network. The proportional hazards regression model constructed by 16 immune genes shows a good predictive ability for the prognosis of bladder urothelial carcinoma.

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“…RPL14, which is overexpressed in CRC [141], further activates the processing of the 12S rRNA to mature 5.8S. 18S pre-rRNA processing is activated by NIN1 (RPN12) binding protein 1 homolog (NOB1) in cooperation with "partner of NOB1" (PNO1) which is overexpressed in CRC [151]. 18S pre-rRNA processing is also activated by human U3 protein (UTP) 14a (hUTP14a), and is overexpressed and constitutes a marker of poor prognosis in CRC [152].…”

Section: Regulation Of Ribosome Biogenesis By Ribosomal Proteins In Crcmentioning

confidence: 99%

Ribosome Biogenesis Alterations in Colorectal Cancer

Slimane

Marcel

Fenouil

et al. 2020

Cells

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Many studies have focused on understanding the regulation and functions of aberrant protein synthesis in colorectal cancer (CRC), leaving the ribosome, its main effector, relatively underappreciated in CRC. The production of functional ribosomes is initiated in the nucleolus, requires coordinated ribosomal RNA (rRNA) processing and ribosomal protein (RP) assembly, and is frequently hyperactivated to support the needs in protein synthesis essential to withstand unremitting cancer cell growth. This elevated ribosome production in cancer cells includes a strong alteration of ribosome biogenesis homeostasis that represents one of the hallmarks of cancer cells. None of the ribosome production steps escape this cancer-specific dysregulation. This review summarizes the early and late steps of ribosome biogenesis dysregulations described in CRC cell lines, intestinal organoids, CRC stem cells and mouse models, and their possible clinical implications. We highlight how this cancer-related ribosome biogenesis, both at quantitative and qualitative levels, can lead to the synthesis of ribosomes favoring the translation of mRNAs encoding hyperproliferative and survival factors. We also discuss whether cancer-related ribosome biogenesis is a mere consequence of cancer progression or is a causal factor in CRC, and how altered ribosome biogenesis pathways can represent effective targets to kill CRC cells. The association between exacerbated CRC cell growth and alteration of specific steps of ribosome biogenesis is highlighted as a key driver of tumorigenesis, providing promising perspectives for the implementation of predictive biomarkers and the development of new therapeutic drugs.

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EBF1-Mediated Upregulation of Ribosome Assembly Factor PNO1 Contributes to Cancer Progression by Negatively Regulating the p53 Signaling Pathway

Cited by 55 publications

References 45 publications

RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1

RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1

Identification of Prognostic Immune Genes in Bladder Urothelial Carcinoma

Ribosome Biogenesis Alterations in Colorectal Cancer

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